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Deficiency of iodide peroxidase(TDH2A)

MedGen UID:
226940
Concept ID:
C1291299
Disease or Syndrome
Synonyms: Congenital Hypothyroidism, TPO-Related; HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 2A; IODIDE PEROXIDASE DEFICIENCY; TDH2A; Thyroid dyshormonogenesis 2A; THYROID HORMONOGENESIS, GENETIC DEFECT IN, 2A; THYROID PEROXIDASE DEFICIENCY
SNOMED CT: Deficiency of iodinase (124204003); Deficiency of iodide peroxidase (124204003)
 
Gene (location): TPO (2p25.3)
 
Monarch Initiative: MONDO:0010133
OMIM®: 274500

Definition

Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). The most prevalent cause of thyroid dyshormonogenesis is TPO deficiency (Park and Chatterjee, 2005). Defects in TPO cause a severe form of congenital hypothyroidism characterized by a complete and immediate release of accumulated radioiodide from the thyroid after sodium perchlorate administration (Bakker et al., 2000). This release of radioiodide represents total iodine organification defect (TIOD), a disruption of the process by which iodide present in the thyroid is oxidized by hydrogen peroxide and bound to tyrosine residues in thyroglobulin (TG; 188450) to form iodotyrosine. [from OMIM]

Additional description

From MedlinePlus Genetics
Congenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital). The thyroid gland is a butterfly-shaped tissue in the lower neck. It makes iodine-containing hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). People with congenital hypothyroidism have lower-than-normal levels of these important hormones.

Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80 to 85 percent of cases, the thyroid gland is absent, severely reduced in size (hypoplastic), or abnormally located. These cases are classified as thyroid dysgenesis. In the remainder of cases, a normal-sized or enlarged thyroid gland (goiter) is present, but production of thyroid hormones is decreased or absent. Most of these cases occur when one of several steps in the hormone synthesis process is impaired; these cases are classified as thyroid dyshormonogenesis. Less commonly, reduction or absence of thyroid hormone production is caused by impaired stimulation of the production process (which is normally done by a structure at the base of the brain called the pituitary gland), even though the process itself is unimpaired. These cases are classified as central (or pituitary) hypothyroidism.

Signs and symptoms of congenital hypothyroidism result from the shortage of thyroid hormones. Affected babies may show no features of the condition, although some babies with congenital hypothyroidism are less active and sleep more than normal. They may have difficulty feeding and experience constipation. If untreated, congenital hypothyroidism can lead to intellectual disability and slow growth. In the United States and many other countries, all hospitals test newborns for congenital hypothyroidism. If treatment begins in the first two weeks after birth, infants usually develop normally.

Congenital hypothyroidism can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic. Some common forms of syndromic hypothyroidism include Pendred syndrome, Bamforth-Lazarus syndrome, and brain-lung-thyroid syndrome.  https://medlineplus.gov/genetics/condition/congenital-hypothyroidism

Clinical features

From HPO
Goiter
MedGen UID:
42270
Concept ID:
C0018021
Disease or Syndrome
An enlargement of the thyroid gland.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Thyroid defect in oxidation and organification of iodide
MedGen UID:
336419
Concept ID:
C1848800
Finding
Decreased circulating T4 concentration
MedGen UID:
1611997
Concept ID:
C4531078
Finding
A reduction below the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).

Professional guidelines

PubMed

Krude H, Kühnen P, Biebermann H
Best Pract Res Clin Endocrinol Metab 2015 Jun;29(3):399-413. Epub 2015 Apr 26 doi: 10.1016/j.beem.2015.04.004. PMID: 26051299
Duntas LH, Papanastasiou L, Mantzou E, Koutras DA
Exp Clin Endocrinol Diabetes 1999;107(6):356-60. doi: 10.1055/s-0029-1212126. PMID: 10543412

Recent clinical studies

Etiology

Wang LF, Sun RX, Li CF, Wang XH
Endokrynol Pol 2021;72(6):666-667. Epub 2021 Aug 11 doi: 10.5603/EP.a2021.0074. PMID: 34378788
Avadhanula S, Introne WJ, Auh S, Soldin SJ, Stolze B, Regier D, Ciccone C, Hannah-Shmouni F, Filie AC, Burman KD, Klubo-Gwiezdzinska J
JAMA Netw Open 2020 Mar 2;3(3):e201357. doi: 10.1001/jamanetworkopen.2020.1357. PMID: 32202644Free PMC Article
Krysiak R, Kowalcze K, Okopień B
J Clin Pharmacol 2019 Nov;59(11):1477-1484. Epub 2019 May 20 doi: 10.1002/jcph.1447. PMID: 31106856
Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979
Drutel A, Archambeaud F, Caron P
Clin Endocrinol (Oxf) 2013 Feb;78(2):155-64. doi: 10.1111/cen.12066. PMID: 23046013

Diagnosis

Avadhanula S, Introne WJ, Auh S, Soldin SJ, Stolze B, Regier D, Ciccone C, Hannah-Shmouni F, Filie AC, Burman KD, Klubo-Gwiezdzinska J
JAMA Netw Open 2020 Mar 2;3(3):e201357. doi: 10.1001/jamanetworkopen.2020.1357. PMID: 32202644Free PMC Article
Hernandez A, Stohn JP
Int J Mol Sci 2018 Jun 19;19(6) doi: 10.3390/ijms19061804. PMID: 29921775Free PMC Article
Suh M, Abraham L, Hixon JG, Proctor DM
J Expo Sci Environ Epidemiol 2014 Nov;24(6):579-87. Epub 2013 Oct 23 doi: 10.1038/jes.2013.67. PMID: 24149973
Glaser B
Pediatr Endocrinol Rev 2003 Dec;1 Suppl 2:199-204; discussion 204. PMID: 16444159
Bozeman PM, Learn DB, Thomas EL
J Immunol Methods 1990 Jan 24;126(1):125-33. doi: 10.1016/0022-1759(90)90020-v. PMID: 2154520

Therapy

Wang LF, Sun RX, Li CF, Wang XH
Endokrynol Pol 2021;72(6):666-667. Epub 2021 Aug 11 doi: 10.5603/EP.a2021.0074. PMID: 34378788
Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979
Kang MJ, Hwang IT, Chung HR
Thyroid 2018 Jun;28(6):773-779. doi: 10.1089/thy.2017.0507. PMID: 29737233
Krude H, Kühnen P, Biebermann H
Best Pract Res Clin Endocrinol Metab 2015 Jun;29(3):399-413. Epub 2015 Apr 26 doi: 10.1016/j.beem.2015.04.004. PMID: 26051299
Wiersinga WM
Clin Endocrinol (Oxf) 2013 Aug;79(2):145-51. Epub 2013 May 11 doi: 10.1111/cen.12222. PMID: 23581474

Prognosis

Monko TR, Tripp EH, Burr SE, Gunderson KN, Lanier LM, Georgieff MK, Bastian TW
J Nutr 2024 Jan;154(1):49-59. Epub 2023 Nov 19 doi: 10.1016/j.tjnut.2023.11.007. PMID: 37984740Free PMC Article
Bruellman RJ, Watanabe Y, Ebrhim RS, Creech MK, Abdullah MA, Dumitrescu AM, Refetoff S, Weiss RE
J Clin Endocrinol Metab 2020 May 1;105(5):1564-72. doi: 10.1210/clinem/dgz297. PMID: 31867598Free PMC Article
Zhao H, Li H, Huang T
Biol Trace Elem Res 2018 Aug;184(2):317-324. Epub 2017 Nov 21 doi: 10.1007/s12011-017-1209-6. PMID: 29164514
Suh M, Abraham L, Hixon JG, Proctor DM
J Expo Sci Environ Epidemiol 2014 Nov;24(6):579-87. Epub 2013 Oct 23 doi: 10.1038/jes.2013.67. PMID: 24149973
Carlé A, Laurberg P, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, Jorgensen T
Eur J Endocrinol 2006 Jan;154(1):21-8. doi: 10.1530/eje.1.02068. PMID: 16381987

Clinical prediction guides

Liu XS, Bai XL, Wang ZX, Xu SY, Ma Y, Wang ZN
Hum Exp Toxicol 2021 Jul;40(7):1163-1172. Epub 2021 Jan 29 doi: 10.1177/0960327121989416. PMID: 33508982
Avadhanula S, Introne WJ, Auh S, Soldin SJ, Stolze B, Regier D, Ciccone C, Hannah-Shmouni F, Filie AC, Burman KD, Klubo-Gwiezdzinska J
JAMA Netw Open 2020 Mar 2;3(3):e201357. doi: 10.1001/jamanetworkopen.2020.1357. PMID: 32202644Free PMC Article
Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979
Wiersinga WM
Clin Endocrinol (Oxf) 2013 Aug;79(2):145-51. Epub 2013 May 11 doi: 10.1111/cen.12222. PMID: 23581474
Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar N, Ray D, Kanwar R, Agarwal R
Br J Nutr 2009 Aug;102(3):382-6. Epub 2009 Feb 10 doi: 10.1017/S0007114509220824. PMID: 19203420

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